| 18039579 |
Kondo T, Nekado T, Sugimoto I, Ochi K, Takai S, Kinoshita A, Hatayama A, Yamamoto S, Kishikawa K, Nakai H, Toda M: Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group. Bioorg Med Chem. 2008 Feb 15;16(4):1613-31. Epub 2007 Nov 17.
A series of (4beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. |
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